Children who are cured of cancer often suffer long-term side effects later in life as a result of the chemotherapy and/or radiotherapy treatment they received. These are also called late effects. Characteristics include symptoms of premature aging and reductions in neurocognitive functions, such as concentration, memory and other thinking-related functions.
Vonk explains her research plans: 'Treatment with chemo- and radiotherapy causes damage to our DNA. Fortunately, the treatments are often successful, but in some children the damage is so high that the repair of this is not efficient enough and the DNA damage accumulates. This accumulation of DNA damage is similar to how we see it happen during aging and in people with dementia. From our research, we know that the accumulation of DNA damage disrupts the proper production of proteins, our body's signaling substances and building blocks. In this project, I am investigating the effects of DNA damage on protein metabolism in the brain.'
More insight into underlying mechanisms
ZonMW is funding the study from their Dementia Research Program. It is expected that the research will also provide insight into the onset and course of dementia, because there are many similarities between the onset of age-related diseases of the brain and neurocognitive side effects.
Vonk: 'Specifically, I'm going to look at how communication between the different cell types of the brain are affected. How does this potentially contribute to the formation of harmful protein clumps? And how might this ultimately lead to nerve death with premature aging and reduction of neurocognitive functions? The results I expect will provide more insight into the underlying mechanisms of late neurocognitive effects in 'survivors' of childhood cancer. In addition, our research may help to understand the onset of dementia in the elderly in more detail.'
National dementia strategy
From the Hoeijmakers group, Vonk is conducting her research as part of a network of Dutch neuroscientists called MODEM (Mechanisms Of DEMentia). Led by VU University Amsterdam professor of neurobiology Guus Smit, this group is investigating which disease mechanisms underlie the aforementioned late effects and dementia, such as Alzheimer's disease (AD), fronto-temporal dementia (FTD), and vascular dementia.
In addition to research institutes, educational institutions, healthcare providers, and industry also participate in the consortium. This also allows new knowledge to quickly reach the clinic and companies working on new treatments. The Dementia Research Program is part of the Ministry of Health, Welfare and Sport's National Dementia Strategy 2021-2030.